[source]
pmid = PMID:30701076
title = Activation of TGF-β signaling in an aortic aneurysm in a patient with Loeys-Dietz syndrome caused by a novel loss-of-function variant of TGFBR1
[diagnosis]
disease_id = OMIM:609192
disease_label = Loeys-Dietz syndrome 1
[text]
The patient was a Japanese man with  his tall stature, thin body habitus (height, 182cm; weight, 43.6 kg),
and scoliosis at the age of 15 years. Echocardiography revealed an enlargement of the sinus of Valsalva
(36 mm; aortic root Z-score4, 5.87), for which he had been followed up at a local hospital.
At the age of 27 years, his aortic root diameter was 41 mm (188 cm; 50 kg; Z-score, 5.17).
He had a positive wrist and thumb sign and presented with pectus excavatum, a hindfoot deformity,
lumbosacral dural ectasia, protrusio acetabuli, kyphoscoliosis, facial features (dolichocephaly,
downslanting palpebral fissures, and malar hypoplasia), skin striae, high myopia, and mitral valve prolapse
(15 points, according to the 2010 revised Ghent nosology5). Furthermore, he had a bifid uvula, hypertelorism,
tortuous cerebral arteries, and cervical spine instability. At the age of 31, his aortic root diameter was 48 mm (Z-score, 8.08),
and his aneurysm was treated using the David valve-sparing root replacement procedure. Extended histological examinations
revealed elastin degradation, cystic medial necrosis, and increased SMAD2 phosphorylation, indicating active TGF-β signaling
in the aortic wall (Fig. 1a, b).